1. Field of Invention
This patent application relates to methods for magnetic resonance imaging and spectroscopy, and more specifically relates to magnetic resonance (MR) methods for assessing tissue metabolism and perfusion using injection of non-toxic and non-labeled substances
2. Discussion of Related Art
Increased glucose uptake is a well-accepted marker of tumor aggression. In general, tumors tend to have higher glucose utilization and uptake than normal tissue. Following malignancy, glucose uptake in tumors increases dramatically. Glucose uptake, as a biomarker, can be measured by Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET), which has become the radiological modality of choice for detecting tumor malignancy. For example, FDG-PET has been proven suitable for detecting and staging primary breast carcinomas and for monitoring response to chemotherapy, as well as many other cancers. However, 18FDG is a radioactive substance with a half-life of 110 minutes, thus requiring a fresh supply. The use of radioactivity limits repeated frequent use in the same person. In addition PET has low spatial resolution compared to CT and MRI and negligible inherent tissue contrast, leading to the need for anatomical co-registration using CT or MRI.
Other important biomarkers of malignancy include increased permeability of the vascular bed and increased microvessel density, which can be assessed using dynamic contrast-enhanced MRI (DCE-MRI). So far, DCE-MRI has been used to determine tumor grade, extent of disease, and treatment response. For example, recent multi-center results from the International Breast MR Consortium trial concluded that the combined use of architectural (shape) and dynamic contrast features increased specificity for breast MRI. DCE-MRI has been used clinically to image tumor perfusion parameters such as vascular volume and permeability from kinetic modeling of the DCE signal intensity curve as a function of time after bolus injection. However, DCE-MRI relies on the injection of paramagnetic agents such as Gadolinium-DiethyleneTriaminePentaacetic Acid (GdDTPA) that affect relaxation contrast. Such agents have recently been criticized for safety issues in persons with kidney disease (Thomsen, H. S. Nephrogenic systemic fibrosis: A serious late adverse reaction to gadodiamide. Eur Radiol 16, 2619-2621, (2006)).
Thus, there is a need in the art for a methodology to measure abnormalities in tissue metabolism, tissue perfusion and tissue pH that does not use potentially toxic or radioactive exogenous agents and yet is capable of generating sufficient contrast to probe such metabolic and vascular and chemical properties of tissue. This would be especially important for studying tumor malignancy and for monitoring the effects of cancer treatment. If developed, this methodology may reduce false-positive detection rates for cancer by functioning as an add-on for current high-volume screening approaches and to improve treatment monitoring. Another application is for assessing cardiovascular disease, where changes in tissue perfusion parameters and pH may occur during ischemia.